P582: AZACITIDINE COMBINED WITH HAG REGIMEN AS INDUCTION THERAPY IN ADULT AML PATIENTS
Authors: Hong Pan, Jingyu Zhao, Zhen Gao, Lele Zhang, LI Weiwang, Liwei Fang, Jun Shi
Journal: HemaSphere (2023)

Background: The CR rate of standard “3 + 7” regimens for de novo acute myeloid leukemia range from 65% to 85%.Chemotherapy combine with targeted drugs like BCL2 inhibitors increase CR rate to 80~90%. Azacitidine(Aza) is commonly used to treat older patients with newly diagnosed AML，The complete remission (CR) rates of Aza combined regimens varied with different drugs. HAG(HHT, low-dose cytarabine, G-CSF) is a so called priming regimen and always used for elderly/unfit AML patients. The efficacy and safety of Aza combined with HAG(HAGA) in adult AML patients are not sure. We prospective enrolled our cohort of patients with AML treated with HAGA regimen. Aims: To explore the efficacy and safety of HAGA regimen in adult AML patient. Methods: We prospectively enrolled 69 patients from June 2019 to Oct 2022 from our centre presenting with AML and fit for chemotherapies. After 2 cycle of HAGA regimens, patients received 2 cycles of moderate doses of cytarabine and 2 cycles of HAGA as consolidation chemotherapy or underwent allo-HSCT. The primary endpoints were 2-year OS rate and 2-year DFS rate. The secondary endpoints were rate of composite complete response (CR+CRi) and rate of MRD negative composite complete response within 2 cycles. Results: Among the 69 AML patients who received HAGA induction therapy, 58 were newly diagnosed (including 22.4% in the ELN2022 high risk group,25.9% in the median risk group), and 9 were relapsed/refractory,1 secondary AML. The median follow-up time was 25.5 months (range:2.5-43.5 months). After the first cycle of HAGA, the composite CR rate were 82.6%(57/69), including 84.5% (49/58) in newly diagnosed patients, 66.7%(10/15) in ELN2022 high risk group and 80% (8/10) in relapsed/refractory patients. The rate of MRD negative CR rate is 47.8%(33/69), including 48.3% (28/58) in newly diagnosed patients, 40%(6/15) in ELN2022 high risk group and 50% (5/10) in R/R patients. 59 patients received a secondary HAGA reinduction/consolidation regimen and were evaluated for efficacy. After the 2th HAGA, the composite CR rate increase to 91.5%(54/59),the MRD-negative composite CR rate rise up to 81.4%(48/59). Especially in high-risk patients, after 2 cycles of HAGA, the composite CR rate was 90.9%(10/11), the MRD-negative composite CR rate was 72.7%(8/11). The overall 2-year OS rate was 66.3%, median OS was 31.7 months (95%CI: 27.6-35.9 months). And the 2-year DFS rate was 57.8%,median EFS was 26.3 months(95%CI: 21.6-31.0 months). As expected, Grade ≥3 toxicities were predominantly hematologic. The median duration of neutropenia was 11 (0-42) days in the first cycle and 6 (0-42) days in the second cycle. Only 1 patient died during induction therapy. Summary/Conclusion: Azacitidine combined with HAG regimen as induction therapy can achieve a high CR rate and MRD negative rate, provide patients with transplantation opportunities and better survival outcomes, and is expected to become the first-line treatment option for adult AML. Keywords: AML, Chemotherapy, Azacitidine